Epidemiology and prevalence of lean nonalcoholic fatty liver disease and associated cirrhosis, hepatocellular carcinoma, and cardiovascular outcomes in the United States: a population‐based study and review of literature

BACKGROUNDS: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and metabolic syndrome conditions. However, a subset of NAFLD patients express a normal or low body mass index (lean NAFLD [L‐NAFLD]). Our aim is to compare the prevalence of L‐NAFLD to the obesity‐associated NAFLD in the United States by assessing prevalence, potential risk factors, liver‐related complications, and coronary artery disease outcomes. METHODOLOGY: A multicenter database (Explorys Inc.) of >70 million patients across the United States was screened. A cohort of patients with “nonalcoholic fatty liver” between 1999 and 2021 was identified. Two sub‐cohorts of NAFLD patients were identified: those with a body mass index (BMI) < 25 kg/m(2) (L‐NAFLD) and those with a BMI > 30 kg/m(2) (obesity‐associated NAFLD). We excluded patients with age <18 and those who have viral hepatitis, hemochromatosis, Wilson's disease, biliary cirrhosis, alcoholic liver disease, cystic fibrosis, alpha‐1‐antitrypsin deficiency, and autoimmune hepatitis. Multivariate analysis was performed to adjust for confounders. RESULTS: 68 892 260 individuals were screened. NAFLD prevalence was four per 100 000, and L‐NAFLD prevalence was 0.6 per 100 000. Compared with those without, patients with L‐NAFLD tended to be older (OR 2.16), females (OR 1.28), and smokers (OR 4.67) and of Asian race (OR 2.12). L‐NAFLD patients were more likely to have acute coronary syndromes (OR 30.00) and metabolic syndrome (OR 2.31) despite the normal/low BMI. Esophageal varices and hepatocellular carcinoma risks were high in both cirrhosis patients. CONCLUSION: This is the largest study to assess L‐NAFLD prevalence in the United States. L‐NAFLD are at a significantly higher risk for acute coronary syndromes, esophageal varices, and hepatocellular carcinoma.